The main aim of the proposed research is to obtain new information about the etiology of insulin-dependent diabetes mellitus (IDDM) in Finland, where the incidence of IDDM is highest in the world and still increasing. It is assumed that understanding why Finland has the highest incidence rate of IDDM in the world and why the incidence rate is still increasing among Finnish children will lead to the determination of the etiology of IDDM. Since genetic susceptibility to IDDM has been measured by complete HLA genotyping and putative environmental determinants have also been measured, there exists an unique opportunity to estimate the interaction between genetic and environmental factors. The investigators' DiMe study represents the largest family study of IDDM with detailed data on epidemiology, HLA genetics and putative environmental risk factors. During the next three years of support requested, the primary goals will be the analysis of the data collected during the previous years of the study. Data on new cases of childhood IDDM registered in Finland nationwide will be used to determine long-term temporal trends, seasonality, spatial variation, and space-time clustering of IDDM. Also, international comparative analyses will be continued. The genetic family data on HLA-A, C, B, DR, DQ markers and entire HLA haplotypes will be analyzed in detail. Attention will be particularly paid to the haplotype versus single allele effects, and to haplotypes transmitted from a parent with IDDM to the child with IDDM. The role of class I antigens for the risk of IDDM will be evaluated in detail. The case-control studies will be analyzed by addressing the role of various dietary factors, viral infections, and vaccinations in the development of IDDM. In utero effects will be investigated in three ways: comparing the birth weight and length in IDDM cases and controls, comparing the reported diet between mothers of cases and controls, and comparing virus antibody levels in sera between the cases and controls collected during pregnancy. New information will be obtained about the role of genetic and environmental factors in the development of IDDM in 9,463 offspring of 5,261 IDDM patients in a population-based prospective study to determine the reasons for sex-associated effects for the transmission of genetic susceptibility to IDDM.